Preparation and applications of novel complexes made by gamma-polyglutamic acid and cisplatin

a technology of polyglutamic acid and complexes, applied in the field of complexes made from gamma-polyglutamic acid and cisplatin, can solve the problems of low yield, high production cost, and limit commercialization

Inactive Publication Date: 2009-04-23
YE HAIFENG +6
View PDF0 Cites 8 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Currently, most γ-PGA polymers are made by synthetic methods which produce low yields and have high production costs which limit commercialization.
However, cisplatin has a very low solubility, low selectivity, and significant toxicity.
Therefore, clinical use of cisplatin significantly limited.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Preparation and applications of novel complexes made by gamma-polyglutamic acid and cisplatin
  • Preparation and applications of novel complexes made by gamma-polyglutamic acid and cisplatin
  • Preparation and applications of novel complexes made by gamma-polyglutamic acid and cisplatin

Examples

Experimental program
Comparison scheme
Effect test

example 1

(1) Method of Preparing γ-PGA-CDDP Complex

[0048]11.4 mg AgNO3 and 20 mg cisplatin were dissolved in 10 ml double distilled water. The resulting solution was allowed to sit for 24 h. then centrifuged to remove the precipitate and filtered through a 0.22 μm membrane to remove fine particulates. 75 mg of small molecule γ-PGA was added to the resulting solution and the pH was adjusted to 7-8. The resulting mixture was mixed at 37° C. for 48 h under no light and then dialyzed for 24 hr to remove un-reacted cisplatin. Lyophilize was used to obtain the γ-PGA-CDDP complex as a white crystalline powder. Based on this procedure, the mole ratio of cisplatin and γ-PGA is 25:1, or m=25. This method of preparing γ-PGA-CDDP complex was used in all of the following examples.

[0049]11.4 mg AgNO3 and 30 mg cisplatin were dissolved in 10 ml double distilled water and was allowed to sit for 24 h. then centrifuged to remove the precipitate and filtered through 0.22 μm membrane to remove fine particulates...

example 2

(1) Use Fermentation to Obtain Large Molecule γ-PGA

[0052]Activate Bacillus Licheniformis ATCC 9945a, was inoculated to a slant culture and incubated at 37° C. for 11 h. The culture includes peptone (10 g / l), NaCl (5 g / l), yeast extract (5 g / l), and agar (20 g / l).

[0053]Culturing: Inoculate the activated bacterial in the cell culture, 37° C., 210 rpm.

[0054]Culturing medium: peptone (10 g / l), NaCl (5 g / l), yeast extract (5 g / l).

[0055]Fermentation medium: peptone (50 g / l), yeast extract (10 g / l), glutamic acid (30 g / l), NaCl (10 g / l), KH2PO4 (5 g / l), and MgSO4.7H2O (0.5 g / l). The fermentation medium was used to fill in a 200 ml / 1000 ml shaking bottle and sterilized at 115° C. for 20 min. After sterilization and cool down, the medium was inoculated with 5% of Bacillus Licheniformis ATCC 9945a and cultured at 37° C. and rotated at 220 rpm. Fermentation was conducted for 48 h.

[0056]After fermentation, distilled water was added to the fermentation aliquot (4 times dilution), the pH was adju...

example 3

Large-Scale Preparation of Small Molecule γ-PGA

[0058]A 2% aqueous solution of the large molecule γ-PGA was prepared and the pH was adjusted to 2˜3. The aliquot was subjected to high temperature and high pressure (121° C., 0.1 MPa) for 15, 20, and 30 min and immediately placed in ice bath. The pH was adjusted to 7˜8. The aliquot was dialyzed and lyophilized to obtain small molecule γ-PGA as a white crystalline powder. An Ubbelohde viscometer to measure the molecular weight of the small molecule γ-PGA which was found to be 80-100 kD, 35-60 kD, or 5-20 kD. Preparation of the small molecule γ-PGA-CDDP complex was the same as in Example 1.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
physicalaaaaaaaaaa
chemical propertiesaaaaaaaaaa
biological compatibilityaaaaaaaaaa
Login to view more

Abstract

A series of complexes made by γ-polyglutamic acid (γ-PGA) and cisplatin, their preparation and applications in biomedical field, specifically in cancer treatment. The complexes may be made by binding free cisplatin on small molecule γ-PGA through the reaction between carboxylic group of γ-PGA and Cl of cisplatin. The complexes show effective anticancer effect and are easy and cost effective to prepare.

Description

TECHNICAL FIELD[0001]The present invention relates to a series of complexes made from γ-polyglutamic acid (γ-PGA) and cisplatin, their preparation and applications in biomedical fields, particularly in cancer treatment.BACKGROUND ART[0002]γ-PGA is a polymer produced by microbial; it can be made by the condensation between the α-amino group and γ-carboxylic group of glutamic acid. γ-PGA was first discovered by Ivanovics et al. (Ivanovics et al., Immunit atsforch. 1937, 90, 304-318) from Bacillus Licheniformis. Subsequently, Bovarnick et al. (Biol Chem. 1942, 145:415) discovered that γ-PGA can be produced by fermentation of some Bacillus Licheniformis. The molecular weight of γ-PGA produced by fermentation ranges between 10 kD and 2000 kD and may be made and separated based on molecular weight ranges for different uses.[0003]γ-PGA consists of a great number of carboxylic groups and is known to form complexes with certain drugs. The complexes can be metabolized to become glutamic acid ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/02C07K2/00A61P35/00A61K33/243
CPCA61K33/24A61K38/02A61K47/48315A61K2300/00A61K47/645A61P35/00A61K33/243
Inventor YE, HAIFENGWU, ZIRONGHUANG, JINGJIN, LIHU, RONGZHANGHE, CHENGLIANGLIU, JIAN
Owner YE HAIFENG
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap